Evidence map›Paper›PMID 8223473›Full record

ArticleThe EMBO journal1993

Mutations of the intronic IgH enhancer and its flanking sequences differentially affect accessibility of the JH locus.

J Chen, F Young, A Bottaro, V Stewart, R K Smith, F W Alt

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 1993. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
8.0field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

57 citing papers in PubMed, 187 citations in OpenAlex.

  1. Article
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  7. The center of accessibility: Dβ control of V(D)J recombination.Archivum immunologiae et therapiae experimentalis · 2010
    Review
  8. Article
  9. Endothelial SUR-8 acts in an ERK-independent pathway during atrioventricular cushion development.Developmental dynamics : an official publication of the American Association of Anatomists · 2010
    Article
  10. Review
  11. Article
  12. Article
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  18. Elucidation of IgH intronic enhancer functions via germ-line deletion.Proceedings of the National Academy of Sciences of the United States of America · 2005
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

J ChenHoward Hughes Medical Institute, Children's Hospital, Boston, MA.
F Young
A Bottaro
V Stewart
R K Smith
F W Alt
Howard Hughes Medical Institute · US

Funding

Mechanisms that Control IgH Variable Region Exon AssemblyR01AI020047 · NIAID · IMMUNE DISEASE INSTITUTE, INC. · PI ALT, FREDERICK W. · 1985 to 2025
$14.1M
ASSEMBLY AND EXPRESSION OF IG VARIBLE REGION GENESR37AI020047 · NIAID · IMMUNE DISEASE INSTITUTE, INC. · PI ALT, FREDERICK W · 1991 to 2000
$323k
MOLECULAR BASIS OF IMMUNE FUNCTION IN HEALTH AND DISEASEU01AI031541 · NIAID · CHILDREN'S HOSPITAL BOSTON · PI GEHA, RAIF SALIM · 1991 to 1994
–
NIAID NIH HHS AI20047NIAID NIH HHS U01 AI31541
6 · The paper itself

Abstract

To investigate the role of intronic immunoglobulin heavy chain (IgH) enhancer (E mu) in generating accessibility of the JH locus for VDJ recombination, we generated ES cells in which E mu or its flanking sequences were mutated by replacement with or insertion of an expressed neor gene. Heterozygous mutant ES cells were used to generate chimeric mice from which pre-B cell lines were derived by transformation of bone marrow cells with Abelson murine leukemia virus (A-MuLV). Comparison of the rearrangement status of the normal and mutated alleles in individual pre-B cell lines allowed us to assay for cis-acting effects of the mutations. Replacement of a 700 bp region immediately downstream from the core E mu [which includes part of the 3' matrix associated region (MAR) and the I mu exon] had no obvious effect on rearrangement of the targeted allele, indicating that insertion of a transcribed neor gene into the JH-C mu intron does not affect JH accessibility. In contrast, replacement of an overlapping 1 kb DNA fragment that contains the E mu resulted in a dramatic cis-acting inhibition of rearrangement, demethylation and germline transcription of the associated JH locus. Surprisingly, insertion of the neor gene into the 5' MAR sequence approximately 100 bp upstream of the core E mu also dramatically decreased recombination of the linked JH locus; but, in many lines, did not prevent demethylation of this locus. We conclude that integrity of the E mu and upstream flanking sequences is required for efficient rearrangement of the JH locus and that demethylation of this locus, per se, does not necessarily make it a good substrate for VDJ recombination.

Indexed as

Enhancer Elements, GeneticAnimalsCell Line, TransformedGene Rearrangement, B-Lymphocyte, Heavy ChainImmunoglobulin Heavy ChainsImmunoglobulin Joining RegionIntronsMethylationMiceMutationRestriction MappingTranscription, GeneticImmunoglobulin Heavy ChainsImmunoglobulin Joining Region

Identifiers

PMID8223473
PMCPMC413901
OpenAlexW1598468393

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.